The aim of this proposal is to study the constraints imposed by genetic location and by the mating system on molecular evolution and variation. This should illuminate basic mechanisms of variation and evolution. Knowledge of these is of significance for the understanding of human genetic disease. The first project will determine the relative rates of evolution of X- chromosomal and autosomal loci in Drosophila. Theory and indirect empirical evidence suggest that the rate of adaptive evaluate may be faster for X-linked genes than for comparable autosomal genes. Theory shows that the of neutral evolution is the same for the two classes, but the rate of substitution of slightly deleterious alleles should be slower for X-linked loci. These predictions will be tested by comparing rates of synonymous and non-synonymous nucleotide substitutions at suitable loci in a species of Drosophila in which autosome carrying these loci have been translocated onto the X-chromosome with rates in species in which the loci are autosomal. In the second project, the effect of breeding system on the level of molecular variation will be studied by examining DNA sequence variation in species of Brassicaceous plants, some of which highly self-fertilizing and others of which are completely outcrossing. Theoretical predictions the high selfing should lead to an almost complete loss of diversity at neutral sites will be tested by comparing patterns of synonymous variation in the two classes of species. The possible action of selection in maintaining variation will be tested by comparing synonymous versus non-synonym variation within and between the two types of species.